This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The SARS-associated Coronavirus is a highly infectious emerging pathogenic virus.We have developed a high-thoughput fluorescence-based enzymatic assay for the essential cysteine proteinase 3clpro. Using this assay we screened a cysteine proteinase focused inhibitor library and identified two compounds which inhibit the enzyme at low micromolar concentrations. These compounds were also tested in a viral replication assay by collaborators and found to inhibit viral replication as well. Finally we are in the process of solving a co-crystal structure of our most promising compound in complex with the proteinase.